Conference Papers / Δημοσιεύσεις σε Συνέδρια

Tumors generate mechanical forces during growth and progression, which are able to compress blood and lymphatic vessels, reducing perfusion rates and creating hypoxia. Tumor vessels—while nourishing the tumor—are usually leaky and tortuous, which further decreases perfusion. Consequently, vessel leakiness together with vessel compression causes a uniformly elevated interstitial fluid pressure that hinder drug delivery and compromise therapeutic outcomes. To enhance treatment efficacy, stress alleviation and vascular normalization strategies have been developed to improve tumor perfusion and drug delivery. Stress alleviation strategy aim to decrease solid stress levels and reopen compressed blood vessels leading to improve perfusion and drug delivery. On the other hand, vascular normalization strategy aims to restore the abnormalities in tumor vasculature by decreasing vessel leakiness and thus enhance drug efficacy. Here, we employed a mathematical model to study the stress alleviation strategy using published experimental data and performing new experiments in mice bearing breast tumors. Specifically, we accounted for variations in tumor hydraulic conductivity, elastic modulus and swelling related to changes in extracellular matrix components induced by the anti-fibrotic and stress alleviating drug, tranilast. We showed that alleviation of mechanical stresses in tumors reduces the tumor interstitial fluid pressure to normal levels and increases the functionality of the tumor vasculature resulted in improved drug delivery and treatment outcome. Finally, we used model predictions to show that vascular normalization can be combined with stress alleviation to further improve therapeutic outcomes.

Tenoxicam (TXM) is an effective anti-inflammatory and analgesic drug, which presents fast photochemical decomposition. In this work in an attempt to investigate the potential β-CD photostabilizing effect on TXM, the photodegradation rate of β-CD complexed drug was monitored under simulated solar irradiation from Xenon arc lamp. The photodegradation was studied at pH 7.5. A new stability indicating Liquid Chromatography method, for TXM in the presence of β-CD was used. According to the obtained results, in the case of free molecules increasing the concentration the photostability is enhanced. The effect of complexation with CDs on the photodegradation rate seems to vary depending on TXM initial concentration. At low TXM concentrations photodecomposition is retarded upon CD complexation, while at high concentrations the process is accelerated. Molecular dimerisation was studied by 1H(1D) NMR and 2D NOESY experiments. 2D ROESY spectra of complexed molecule were evaluated in order to confirm the complexation. TXM dimers could be considered as a critical parameter affecting oxicams photostability, in combination with the already described ESIPT phenomenon.

Rheumatoid arthritis is a chronic inflammatory disorder whose origin of defect has been the subject of extensive research during the past few decades. While a number of immune and non-immune cell types participate in the development of chronic destructive inflammation in the arthritic joint, synovial fibroblasts have emerged as key effector cells capable of modulating both joint destruction and propagation of inflammation. Ample evidence of aberrant changes in the morphology and biochemical behaviour of rheumatoid arthritis synovial fibroblasts have established the tissue evading and "transformed" character of this cell type. We have recently demonstrated that actin cytoskeletal rearrangements determine the pathogenic activation of synovial fibroblasts in modelled TNF-mediated arthritis, a finding correlating with similar gene expression changes which we observed in human rheumatoid arthritis synovial fibroblasts. Here, we show that pharmacological inhibition of actin cytoskeleton dynamics alters potential pathogenic properties of the arthritogenic synovial fibroblast, such as proliferation, migration and resistance to apoptosis, indicating novel opportunities for therapeutic intervention in arthritis. Recent advances in this field of research are reviewed and discussed.

A new onalytical procedure, combining sample pretreatment with solid phase extroction ond high performonce liquid chromatography, was developed and opplied to ketoprofen:cyclodextrin (CD) complexes. The significont differences in molar absorptivity between free and CD bound drugs leod to analytical errors up to 30%. Procedures routinely used to remove most of the common excipients proved to be inadequate, creating the necessity of more specific (HPLC) onalytical methods including the step of dissociotion ond separation of drugs from CDs before the quontitation by UV detector. In the case of complexes such as Ketoprofen: CDs, strong binding to CDs inhibits the dissociation. Prior to the anolysis, the addition of molecules competing the binding in the CD cavity fairly decreased the strength of the complexation. When molecules, competing the binding to CD such os 1-odomantanol, were added to the samples the results were improved. The extent of the selective binding and the drug displocement were monitored with 1H-NMR spectroscopy and it was revealed that only partial dissociation of the complexes was obtained. The combination of the sample pre-treatment with a solid phase extraction technique was proved to be inevitable for the dissociation of the complex. When analyzing supramolecules spectral changes, arising from intramolecular and/or intermolecular interactions, are expected. Cansequently, analytical methods utilized should be carefully revised.

Single molecule magnets are of great interest due to a multitude of potential applications for some of which thin films are required. Traditional physical vapor deposition techniques are not suitable for the deposition of these fragile materials with low decomposition temperatures. Matrix Assisted Pulsed Laser Evaporation technique has been employed for the growth of thin films of the single molecule magnet Mn 12(Propionate) on Si and glass substrates. In this paper we report on the appropriate growth conditions and also the morphology, chemical composition and magnetic behavior of the films. Continuous Mn 12(Propionate) films with properties similar to bulk materials have been obtained.